Bacterial cells utilize both two-component signaling proteins and alternative sigma (?) factors to modulate transcription in response to environmental stress. These environmental stress regulatory proteins are known to function as essential virulence factors in numerous bacterial pathogens. Bacterial stress responses play a fundamental role in bacterial growth, biofilm formation, pathogenesis and symbiosis. My proposed structural studies on the Caulobacter crescentus general stress signaling pathway, which integrates feature of two-component signaling and alternative s regulation, will significantly enhance our understanding of the molecular and structural basis of stress adaptation in the alphaproteobacteria. The Crosson lab has a successful track record utilizing techniques from a wide range of disciplines to pursue questions focused on molecular microbial physiology. Their broad interdisciplinary approaches promise to provide a more complete understanding of how bacterial cells can perceive and adapt to changes within their environment. My postdoctoral training in the Crosson Lab, focused on molecular biophysics and structural biology of the PhyR, ?T and NepR proteins, will facilitate my successful transition into an independent faculty position, where my research will center on molecular aspects of microbial signaling.
The novel general stress regulator, PhyR, is a hybrid signaling protein that integrates two-component and s regulation in the alpha family of proteobacteria. My mechanistic analysis of stress signaling in the Caulobacter model system will provide a detailed understanding of this conserved stress signaling protein and may inform new treatments for a-proteobacterial infection.
|Herrou, Julien; CzyÅ¼, Daniel M; Willett, Jonathan W et al. (2016) WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System. J Bacteriol 198:1281-93|
|Willett, Jonathan W; Crosson, Sean (2016) Atypical modes of bacterial histidine kinase signaling. Mol Microbiol :|
|Willett, Jonathan W; Herrou, Julien; CzyÅ¼, Daniel M et al. (2016) Brucella abortus Î”rpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis. Vaccine 34:5073-81|
|Herrou, Julien; Willett, Jonathan W; Crosson, Sean (2015) Structured and Dynamic Disordered Domains Regulate the Activity of a Multifunctional Anti-Ïƒ Factor. MBio 6:e00910|
|Willett, Jonathan W; Herrou, Julien; Briegel, Ariane et al. (2015) Structural asymmetry in a conserved signaling system that regulates division, replication, and virulence of an intracellular pathogen. Proc Natl Acad Sci U S A 112:E3709-18|
|Kim, Hye-Sook; Willett, Jonathan W; Jain-Gupta, Neeta et al. (2014) The Brucella abortus virulence regulator, LovhK, is a sensor kinase in the general stress response signalling pathway. Mol Microbiol 94:913-25|